Bone Metastases and Osteoporosis

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1 Diagnosis and Treatment of Patients with Primary and Metastatic Breast Cancer Bone Metastases and Osteoporosis

2 Bone Metastases Version 2002: Dall / Fersis / Friedrich Version : Bischoff / Böhme / Brunnert / Diel / Friedrichs / Maas / Oberhoff / Schaller / Seegenschmiedt / Solomayer / Souchon Version 2010: Solomayer / Schaller

3 Bisphosphonates in Breast Cancer Hypercalcemia 1a A ++ Reduction sceletal events (complications) 1a A ++ Treatment beyond progression of bone met s 5 D ++ Prevention of bone metastases Primary breast cancer 1b B +* Advanced breast cancer 2b C +/- Tumor Therapy-Induced Osteoporosis Prevention 1b B ++ Therapy 1b B ++ Prevention and Therapy of Tumor Therapy-Induced 1b B + Bone Loss * Study participation recommended

4 Skeletal Metastasis Treatment with Radionuclids Tumor progression after standard treatment of multiple / disseminated metastases and intolerable bone pain 1b B Rhenium-hydroxyethylidenediphosphonat (z.b. 186 Re-HEDP) 2b B Samarium 1b B + 89 Strontium (z.b. Sr 89 ) 1b B + Cave: Myelosuppression with risks of pancytopenia has to balance potential benefits.

5 Bone Metastases Acute Spinal Cord Compression / Paraplegia Decompression surgery, reduction of tumor volume, stabilisation surgery (< 24 h) and irradiation of the spine (RT) 2b C ++ Irradiation of the spine (< 24 h) +/- steroids 3b C ++ Immediate start of treatment 1c D ++ Clinical trials have included patients with different tumor entities!

6 Prognostic Factors Outcome of Spinal Cord Compression Oxford LoE: 2b GR: B Mobility before therapy Time interval from onset of neurological symptoms and start of therapy Rades et al, Prognostic factors predicting functional outcomes, recurrence-free Survival, and overall survival after radiotherapy for metastatic spinal cord compression in breast cancer patients. Int J Radiat Oncol Biol Phys 2006; 64:

7 Metastatic Bone Disease of the Spine Indications for surgery Oxford LoE: 2b GR: C AGO: ++ Spinal cord compression With progressive neurological symptoms With pathological fractures Instability of the spine Lesions in pre-irradiated parts of the spine

8 Surgery for Bone Metastases Spine and limbs Oxford LoE: 3b GR: C AGO: ++ Marrow splints Osteosynthesis Bone replacement by PMMA or titanspacer Endoprothesis Vertebroplasty / Kyphoplasty Resection of involved bone in oligometastatic disease (sternum, ribs, vertebral bodies)

9 Metastatic Bone Disease: Radiotherapy Bone metastases With fracture risk 1a B ++ With functional impairment 1a B ++ With bone pain 1a B ++ Single RT = fractionated RT 2a B ++ With neuropathic bone pain 1b B ++ Asymptomatic isolated bone metastases 5 D +/- Only few studies included breast cancer patients!

10 Metastatic Bone Disease Recurrent Bone Pain Recurrent bone pain in pre-irradiated parts of the skeleton Single RT (1 x 8 gy) 3b C ++ Fractionated RT (6 x 4 gy)! 3b C + Radionuclid therapy 3b C +

11 Prevention and Therapy of Tumor Therapy-Induced Bone Loss Regular BMD-measurement recommended 2b B + Bisphosphonates 1b B + RANK-ligand antibody 2b B + HRT (independent from ER-status of BC) 5 D - Some data derived from steroid induced bone loss*: Physical activity 4 C ++ Calcium and vitamine D suppl. 4 C ++ Avoiding BMI < 18 3b C ++ *Fischer M. Leitlinie für die Radionuklidtherapie bei schmerzhaften Knochenmetastasen. Nuklearmedizin 1999;38:

12 Prevention of Tumor Therapy-Induced Osteoporosis Regular BMD-measurement recommended 2b B + Bisphosphonates 1b B ++ HRT (independent from ER-status of BC) 5 D -

13 Therapy of Tumor Therapy-induced Osteoporosis Bisphosphonates 1b B ++ HRT (independent from ER-status of BC) 5 D - Some data derived from steroid induced bone loss*: Physical activity 4 C ++ Calcium and vitamine D suppl. 4 C ++ Avoiding BMI < 18 3b C ++ *Fischer M. Leitlinie für die Radionuklidtherapie bei schmerzhaften Knochenmetastasen. Nuklearmedizin 1999;38:

14 Bisphosphonates For Therapy of Bone Metastases Clodronate PO 1600 mg daily 2b B ++ Clodronate IV 1500 mg q3w / q4w 2b B ++ Pamidronate IV 90 mg q3w / q4w 2b B ++ Ibandronate IV 6 mg q3w / q4w 2b B ++ Ibandronate PO 50 mg daily 2b B ++ Zoledronate IV 4 mg q4w 2b B ++ Other doses or schedules, e.g. derived from studies of adjuvant therapy or therapy of osteoporosis 5 D - -

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